Evidence map›Paper›PMID 36882501›Full record

ArticleMolecular psychiatry2023

Genome-wide significant risk loci for mood disorders in the Old Order Amish founder population.

Elizabeth M Humphries, Kwangmi Ahn, Rachel L Kember, Fabiana L Lopes, Evelina Mocci, Juan M Peralta, John Blangero, David C Glahn, Fernando S Goes, Peter P Zandi and 9 more

Open access · greenAbstract read
In one paragraph

Article in Molecular psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.2field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 7 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 7 institutions in 2 countries.

Elizabeth M HumphriesInstitute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
Kwangmi AhnIntramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
Rachel L KemberDepartment of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-8820-2659
Fabiana L LopesIntramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
Evelina MocciInstitute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
Juan M PeraltaUniversity of Texas Rio Grande Valley, Harlingen, TX, USA.ORCID 0000-0002-8811-5579
John BlangeroUniversity of Texas Rio Grande Valley, Harlingen, TX, USA.ORCID 0000-0001-6250-5723
David C GlahnBoston Children's Hospital, Boston, MA, USA.
Fernando S GoesDepartments of Epidemiology and Mental Health, Johns Hopkins School of Medicine, Baltimore, MD, USA.ORCID 0000-0001-6262-8264
Peter P ZandiDepartments of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.ORCID 0000-0001-8423-2623
Peter KochunovDepartment of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA.
Cristopher Van HoutRegeneron Genetics Center, Tarrytown, NY, USA.
Alan R ShuldinerRegeneron Genetics Center, Tarrytown, NY, USA.
Toni I PollinDepartment of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Braxton D MitchellDepartment of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Maja BucanDepartment of Genetics, University of Pennsylvania, Philadelphia, PA, USA.
L Elliot HongDepartment of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA.
Francis J McMahonIntramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.ORCID 0000-0002-9469-305X
Seth A AmentInstitute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA. sament@som.umaryland.edu.ORCID 0000-0001-6443-7509
University of Maryland, Baltimore · USNational Institute of Mental Health · USJohns Hopkins University · USThe University of Texas Rio Grande Valley · USUniversity of Pennsylvania · USAutonomous University of Queretaro · MXBoston Children's Hospital · US

Funding

Translational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI A. Clementina Mesaros · 2006 to 2026
$35.3M
Identification of Genes Involved in Major Mood DisordersZIAMH002843 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI MCMAHON, FRANCIS J · 2009 to 2025
$24.5M
SOLAR-Eclipse Computational Tools for Imaging GeneticsR01EB015611 · NIBIB · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI KOCHUNOV, PETER V. · 2012 to 2024
$5.0M
Amish Connectome Project on Mental IllnessU01MH108148 · NIMH · UNIVERSITY OF MARYLAND BALTIMORE · PI HONG, L ELLIOT ELLIOT, KOCHUNOV, PETER V. · 2015 to 2018
$4.3M
2/3: Pedigree-Based Whole Genome Sequencing of Affective and Psychotic DisordersU01MH105632 · NIMH · UNIVERSITY OF TEXAS RIO GRANDE VALLEY · PI BLANGERO, JOHN · 2015 to 2018
$4.2M
Towards Multisystem-Brain Successful Aging in Schizophrenia SpectrumR01MH116948 · NIMH · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI HONG, L ELLIOT ELLIOT · 2018 to 2022
$3.7M
Genomic analysis of bipolar disorder in a genetic isolateR01MH093415 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI BUCAN, MAJA · 2011 to 2014
$3.5M
Lifespan Vascular Biology on White MatterRF1NS114628 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI HONG, L ELLIOT ELLIOT, KOCHUNOV, PETER V. · 2020 to 2020
$3.1M
The Bipolar Sequencing Consortium for Combined Analyses and Follow-Up - SupplementR01MH110437 · NIMH · JOHNS HOPKINS UNIVERSITY · PI BOEHNKE, MICHAEL L, FREIMER, NELSON B. · 2016 to 2018
$2.5M
The Vascular Axis in Schizophrenia Brain-Body AgingR01MH133812 · NIMH · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI L Elliot Elliot Hong · 2024 to 2026
$2.2M
Multi-scale consequences of variants in the schizophrenia risk gene SETD1A in a population isolate.R01MH129343 · NIMH · UNIVERSITY OF MARYLAND BALTIMORE · PI Seth Abrams Ament · 2022 to 2026
$1.9M
1/3:Pedigree-Based Whole Genome Sequencing of Affective and Psychotic DisordersU01MH105630 · NIMH · YALE UNIVERSITY · PI GLAHN, DAVID C · 2015 to 2018
$1.4M
Intramural NIH HHS ZIA MH002843NIBIB NIH HHS R01 EB015611NIEHS NIH HHS P30 ES013508NIH HHS S10 OD023696NIMH NIH HHS R01 MH093415NIMH NIH HHS R01 MH110437NIMH NIH HHS R01 MH116948NIMH NIH HHS R01 MH129343NIMH NIH HHS R01 MH133812NIMH NIH HHS RF1 MH123163NIMH NIH HHS U01 MH105630NIMH NIH HHS U01 MH105632NIMH NIH HHS U01 MH108148NINDS NIH HHS R01 NS114628NINDS NIH HHS RF1 NS114628
6 · The paper itself

Abstract

Genome-wide association studies (GWAS) of mood disorders in large case-control cohorts have identified numerous risk loci, yet pathophysiological mechanisms remain elusive, primarily due to the very small effects of common variants. We sought to discover risk variants with larger effects by conducting a genome-wide association study of mood disorders in a founder population, the Old Order Amish (OOA, n = 1,672). Our analysis revealed four genome-wide significant risk loci, all of which were associated with >2-fold relative risk. Quantitative behavioral and neurocognitive assessments (n = 314) revealed effects of risk variants on sub-clinical depressive symptoms and information processing speed. Network analysis suggested that OOA-specific risk loci harbor novel risk-associated genes that interact with known neuropsychiatry-associated genes via gene interaction networks. Annotation of the variants at these risk loci revealed population-enriched, non-synonymous variants in two genes encoding neurodevelopmental transcription factors, CUX1 and CNOT1. Our findings provide insight into the genetic architecture of mood disorders and a substrate for mechanistic and clinical studies.

Indexed as

AmishGenetic Predisposition to DiseaseGenome-Wide Association StudyMood DisordersPolymorphism, Single NucleotideAdultAgedCase-Control StudiesFemaleFounder EffectGenetic LociHomeodomain ProteinsHumansMaleMiddle AgedNuclear ProteinsHomeodomain ProteinsNuclear ProteinsRepressor ProteinsTranscription Factors

Identifiers

PMID36882501
PMCPMC10483025
OpenAlexW4323355606

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.